Packaging, not yield, may be problem for nasal-spray H1N1 vaccine

Jul 30, 2009 (CIDRAP News) – While most vaccine manufacturers have reaped below-average crops of H1N1 influenza vaccine virus from the eggs in which they're grown, MedImmune Inc. has a different problem: high virus yields, but a potential shortage of the devices used to spray the vaccine into the nose.

The company has produced more than 20 million bulk doses of the vaccine, well above the 12.8 million ordered so far by the US government, and has the capacity to make 205 million bulk doses, said Ben Machielse, executive vice president of operations, in an interview this week.

But he said the company has the capability to put only 41 million doses in sprayers, so it is looking into the possibility of using droppers instead—an option that would require additional regulatory review but may permit making more vaccine available sooner. The Maryland-based company, part of AstraZeneca, makes the seasonal vaccine FluMist, which uses a live but weakened virus.

The other manufacturers that have H1N1 vaccine orders from the Department of Health and Human Services (HHS)—Sanofi Pasteur, Novartis, GlaxoSmithKline (GSK), and CSL Biotherapies—have reported that their virus yields so far have been half or less of what they usually get when growing seasonal flu vaccines. (Yesterday an HHS official said yields have improved somewhat, but gave no details.)

What the low yields mean for production expectations has been unclear. Three of the manufacturers (Sanofi, Novartis, and GSK), when contacted recently by CIDRAP News, declined to say how many doses they expect to make or how many have been ordered by HHS. A Bloomberg News report yesterday, citing Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Novartis is responsible for 45% percent of the supply, while Sanofi will provide 26% and CSL will make 19%.

Meanwhile, MedImmune is getting yields as good as or better than it reaps with seasonal vaccine, according to Machielse. "Given the fact that you need a very, very small dose of FluMist, we get a yield of about 80 doses per egg for this strain, and normally the seasonal strain has a yield of 60 to 100 doses per egg," he said.

MedImmune's better yields may have to do with the fact that the company is using a different seed strain of H1N1, according to Machielse. The injectable-vaccine makers reportedly have been working with a strain developed at New York Medical College. He said MedImmune developed its own strain, combining genes from a wild-type H1N1 virus with the "backbone" genes of the virus used in FluMist.

Machielse said HHS officials have expressed interest in ordering additional MedImmune doses beyond the initial 12.8 million but haven't done so yet. In anticipation of a possible need to supply more doses than it has sprayers for, the company is looking into the dropper option.

"The initial clinical development of FluMist was based on dropper administration, so we have a lot of clinical data on dropper administration," he said. "We've contacted BARDA [HHS's Biological Advanced Research and Development Agency], FDA [the Food and Drug Administration], and the National Vaccine Program Office, and they're working with us to define a regulatory pathway to get a dropper device approved as soon as possible. We have a rough outline of what needs to be done, and we're now in discussion with FDA to fine-tune it."

He said the company has told federal officials it could potentially have multidose droppers of its vaccine ready starting in early October. "We are currently working through all the details with suppliers, FDA, and BARDA to see what needs to be done to get to that point, but there are no guarantees because there are many parties involved," he added.

William Schaffner, MD, an immunization expert and chair of the Department of Preventive Medicine at Vanderbilt University in Nashville, said increased availability of MedImmune's vaccine could help in the effort to immunize children against the new virus. Yesterday the CDC's immunization advisory committee recommended vaccination for young people from 6 months through 24 years old, along with several other groups.

"As a company they've really focused on children, so there's a real potential this could be used widely not only in pediatricians' offices, but if there are a number of school-based flu immunization programs, FluMist is vastly better than injectable vaccine in a school-based program," Schaffner said.

He said the vaccine, being needle-free, is much easier to administer in large numbers than injectable vaccines.

The seasonal version of FluMist is considerably more expensive than injectable flu vaccines. But Schaffner noted that the H1N1 vaccines are being purchased by the federal government, so the cost for recipients or their insurers will mainly be the administrative expense.

The administrative costs may be a barrier to school-based immunization programs, which are typically run by local health departments and take "a fair amount of preparation," Schaffner added.

As for possible adult use of MedImmune's H1N1 vaccine, Schaffner noted that seasonal FluMist has not been used very widely in adults. It is approved for healthy people from ages 2 through 49.

"People who have underlying illnesses can't take FluMist," Schaffner said. That would appear to rule out one of the groups the CDC committee targeted for H1N1 vaccination: those between 25 and 64 who have chronic medical conditions.